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Tauopathy is known to be a major pathognomonic finding in important neurodegenerative diseases such as progressive supranuclear palsy (PSP) and corticobasal degeneration. However, the mechanism by which tauopathy is triggered remains to be elucidated. We previously identified the point mutation c.11596C > G, p.Pro3866Ala in the Bassoon gene (BSN) in a Japanese family with PSP-like syndrome. We showed that mutated BSN may have been involved in its own insolubilization and tau accumulation. Furthermore, BSN mutations have also been related to various neurological diseases. In order to further investigate the pathophysiology of BSN mutation in detail, it is essential to study it in mouse models. We generated a mouse model with the mouse Bassoon p.P3882A mutation, which corresponds to the human BSN p.P3866A mutation, knock-in (KI) and we performed systematic behavioral and histological analyses. Behavioral analyses revealed impaired working memory in a Y-maze test at 3 months of age and decreased locomotor activity in the home cage at 3 and 12 months of age in KI mice compared to those in wild-type mice. Although no obvious structural abnormalities were observed at 3 months of age, immunohistochemical studies showed elevation of Bsn immunoreactivity in the hippocampus and neuronal loss without tau accumulation in the substantia nigra at 12 months of age in KI mice. Although our mice model did not show progressive cognitive dysfunction and locomotor disorder like PSP-like syndrome, dopaminergic neuronal loss was observed in the substantia nigra in 12-month-old KI mice. It is possible that BSN mutation may result in dopaminergic neuronal loss without locomotor symptoms due to the early disease stage. Thus, further clinical course can induce cognitive dysfunction and locomotor symptoms.
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Taste and health are critical factors to be considered when choosing foods. Prioritizing healthiness over tastiness requires self-control. It has also been suggested that self-control is guided by cognitive control. We then hypothesized that neural mechanisms underlying healthy food choice are associated with both self-control and cognitive control. Human participants performed a food choice task and a working memory task during functional MRI scanning. Their degree of self-control was assessed behaviorally by the value discount of delayed monetary rewards in intertemporal choice. Prioritizing healthiness in food choice was associated with greater activity in the superior, dorsolateral, and medial prefrontal cortices. Importantly, the prefrontal activity was greater in individuals with smaller delay discounting (i.e. high self-control) who preferred a delayed larger reward to an immediate smaller reward in intertemporal choice. On the other hand, working memory activity did not show a correlation with delay discounting or food choice activity, which was further supported by supplementary results that analyzed data from the Human Connectome Project. Our results suggest that the prefrontal cortex plays a critical role in healthy food choice, which requires self-control, but not working memory, for maximization of reward attainments in a remote future.
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Conducta de Elección , Descuento por Demora , Preferencias Alimentarias , Imagen por Resonancia Magnética , Memoria a Corto Plazo , Corteza Prefrontal , Recompensa , Humanos , Memoria a Corto Plazo/fisiología , Corteza Prefrontal/fisiología , Corteza Prefrontal/diagnóstico por imagen , Masculino , Femenino , Adulto Joven , Adulto , Conducta de Elección/fisiología , Preferencias Alimentarias/fisiología , Descuento por Demora/fisiología , Dieta Saludable/psicología , Autocontrol , ConectomaRESUMEN
Microdroplet-based fluidic systems have the advantages of small size, short diffusion time, and no cross-contamination; consequently, droplets often provide a fast and precise reaction environment as well as an analytical environment for individual molecules. In order to handle diverse reactions, we developed a method to create organic single-micron droplets (S-MDs) smaller than 5 µm in diameter dispersed in silicone oil without surfactant. The S-MD generation microflow device consists of a mother droplet (MoD) generator and a tapered separation channel featuring multiple side channels. The tapered channel enhanced the shear forces to form tails from the MoDs, causing them to break up. Surface treatment with the fluoropolymer CYTOP protected PDMS fluid devices from organic fluids. The tailing separation of methanol droplets was accomplished without the use of surfactants. The generation of tiny organic droplets may offer new insights into chemical separation and help study the scaling effects of various chemical reactions.
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Deciding whether to wait for a future reward is crucial for surviving in an uncertain world. While seeking rewards, agents anticipate a reward in the present environment and constantly face a trade-off between staying in their environment or leaving it. It remains unclear, however, how humans make continuous decisions in such situations. Here, we show that anticipatory activity in the anterior prefrontal cortex, ventrolateral prefrontal cortex, and hippocampus underpins continuous stay-leave decision-making. Participants awaited real liquid rewards available after tens of seconds, and their continuous decision was tracked by dynamic brain activity associated with the anticipation of a reward. Participants stopped waiting more frequently and sooner after they experienced longer delays and received smaller rewards. When the dynamic anticipatory brain activity was enhanced in the anterior prefrontal cortex, participants remained in their current environment, but when this activity diminished, they left the environment. Moreover, while experiencing a delayed reward in a novel environment, the ventrolateral prefrontal cortex and hippocampus showed anticipatory activity. Finally, the activity in the anterior prefrontal cortex and ventrolateral prefrontal cortex was enhanced in participants adopting a leave strategy, whereas those remaining stationary showed enhanced hippocampal activity. Our results suggest that fronto-hippocampal anticipatory dynamics underlie continuous decision-making while anticipating a future reward.
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Anticipación Psicológica , Toma de Decisiones , Hipocampo , Imagen por Resonancia Magnética , Corteza Prefrontal , Recompensa , Humanos , Masculino , Hipocampo/fisiología , Femenino , Toma de Decisiones/fisiología , Anticipación Psicológica/fisiología , Corteza Prefrontal/fisiología , Adulto Joven , Adulto , Mapeo EncefálicoRESUMEN
This review presents a comprehensive evaluation for the manufacture of organic molecules via efficient microfluidic synthesis. Microfluidic systems provide considerably higher control over the growth, nucleation, and reaction conditions compared with traditional large-scale synthetic methods. Microfluidic synthesis has become a crucial technique for the quick, affordable, and efficient manufacture of organic and organometallic compounds with complicated characteristics and functions. Therefore, a unique, straightforward flow synthetic methodology can be developed to conduct organic syntheses and improve their efficiency.
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Environmental microorganisms possess enzymes that can digest macromolecules such as agarose into smaller molecules that can be utilized for growth. These enzymes could be valuable for the effective utilization of global resources. However, since most of the microorganisms on Earth remain uncultured, there is significant untapped enzymatic potential in nature. Therefore, it is necessary to develop innovative tools and strategies for exploring these enzymatic resources. To address this, we developed a method for screening microbial cells that secrete hydrogel-degrading enzymes using deformability-based microfluidic microdroplet sorting. In this method, microbial cells are encapsulated as single cells in water-in-oil (W/O) microdroplets with a hydrogel whose shape becomes deformable as the hydrogel is progressively degraded into smaller molecules. Screening is achieved using a microfluidic device that passively sorts the deformed W/O microdroplets. Using this method, we successfully sorted agarose-containing microdroplets, encapsulating single bacterial cells that hydrolyzed agarose. This method can be used to screen various hydrogel-degrading microbial cells.
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Hidrogeles , Microfluídica , Microfluídica/métodos , Sefarosa , Bacterias , AguaRESUMEN
A 74-year-old man experienced diplopia, generalized muscle weakness, and acute respiratory failure. He was diagnosed with Lambert-Eaton myasthenic syndrome (LEMS) and treated with immunotherapy, but no improvement was observed, and additional symptoms, including central apnea and hallucinations, appeared. Subsequent serum and cerebrospinal fluid (CSF) analyses confirmed the presence of GABAB receptor antibodies, indicating the coexistence of autoimmune encephalitis. Although there were no findings of malignancy, it is highly likely that occult small-cell lung carcinoma was present. When atypical symptoms occur in patients with LEMS, it is important to consider the possibility of concomitant autoimmune encephalitis.
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The efficient synthesis of amino acid Schiff base copper(II) complexes using a microfluidic device was successfully achieved. Schiff bases and their complexes are remarkable compounds due to their high biological activity and catalytic function. Conventionally, products are synthesized under reaction conditions of 40 °C for 4 h using a beaker-based method. However, in this paper, we propose using a microfluidic channel to enable quasi-instantaneous synthesis at room temperature (23 °C). The products were characterized using UV-Vis, FT-IR, and MS spectroscopy. The efficient generation of compounds using microfluidic channels has the potential to significantly contribute to the efficiency of drug discovery and material development due to high reactivity.
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OBJECTIVES: In 2016, brief resolved unexplained events (BRUEs) were proposed as alternative concepts to apparent life-threatening event (ALTE). The clinical utility of managing ALTE cases according to the BRUE classification is controversial. To verify the clinical utility of the BRUE criteria, we evaluated the proportion of ALTE patients who met and those who did not meet the BRUE criteria and assessed the diagnoses and outcomes of each group. METHODS: We retrospectively investigated patients with ALTE younger than 12 months who visited the emergency department of the National Center for Child Health and Development from April 2008 to March 2020. The patients were classified into the higher-risk and lower-risk BRUE groups; however, those who did not meet the BRUE criteria were classified into the ALTE-not-BRUE group. We evaluated the diagnoses and outcomes of each group. Adverse outcomes included death, recurrence, aspiration, choking, trauma, infection, convulsions, heart disease, metabolic disease, allergies, and others. RESULTS: Over the period of 12 years, a total of 192 patients were included, among which 140 patients (71%) were classified into the ALTE-not-BRUE group, 43 (22%) into the higher-risk BRUE group, and 9 (5%) into the lower-risk BRUE group. Adverse outcomes occurred in 27 patients in the ALTE-not-BRUE group and 10 patients in the higher-risk BRUE group. No adverse outcome occurred in the lower-risk BRUE group. CONCLUSIONS: Many of the patients with ALTE were classified into the ALTE-not-BRUE group, suggesting that replacing ALTE with BRUE is difficult. Although patients classified as lower-risk BRUE showed no adverse outcomes, there were only a few of them. In the pediatric emergency medicine setting, the BRUE risk classification may be beneficial for certain patients.
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Obstrucción de las Vías Aéreas , Evento Inexplicable, Breve y Resuelto , Enfermedades del Recién Nacido , Recién Nacido , Niño , Humanos , Lactante , Estudios Retrospectivos , Factores de RiesgoRESUMEN
In this study, we developed a comb-shaped microfluidic device that can efficiently trap and culture a single cell (bacterium). Conventional culture devices have difficulty in trapping a single bacterium and often use a centrifuge to push the bacterium into the channel. The device developed in this study can store bacteria in almost all growth channels using the flowing fluid. In addition, chemical replacement can be performed in a few seconds, making this device suitable for culture experiments with resistant bacteria. The storage efficiency of microbeads that mimic bacteria was significantly improved from 0.2% to 84%. We used simulations to investigate the pressure loss in the growth channel. The pressure in the growth channel of the conventional device was more than 1400 PaG, whereas that of the new device was less than 400 PaG. Our microfluidic device was easily fabricated by a soft microelectromechanical systems method. The device was highly versatile and can be applied to various bacteria, such as Salmonella enterica serovar Typhimurium and Staphylococcus aureus.
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Both coronavirus disease 2019 (COVID-19) and heat stroke have symptoms of fever or hyperthermia and the difficulty in distinguishing them could lead to a strain on emergency medical care. To mitigate the potential confusion that could arise from actions for preventing both COVID-19 spread and heat stroke, particularly in the context of record-breaking summer season temperatures, this work offers new knowledge and evidence that address concerns regarding indoor ventilation and indoor temperatures, mask wearing and heat stroke risk, and the isolation of older adults. Specifically, the current work is the second edition to the previously published guidance for handling heat stroke during the COVID-19 pandemic, prepared by the "Working group on heat stroke medical care during the COVID-19 epidemic," composed of members from four organizations in different medical and related fields. The group was established by the Japanese Association for Acute Medicine Heatstroke and Hypothermia Surveillance Committee. This second edition includes new knowledge, and conventional evidence gleaned from a primary selection of 60 articles from MEDLINE, one article from Cochrane, 13 articles from Ichushi, and a secondary/final selection of 56 articles. This work summarizes the contents that have been clarified in the prevention and treatment of infectious diseases and heat stroke to provide guidance for the prevention, diagnosis, and treatment of heat stroke during the COVID-19 pandemic.
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We developed a microfluidic device that enables selective droplet extraction from multiple droplet-trapping pockets based on dielectrophoresis. The device consists of a main microchannel, five droplet-trapping pockets with side channels, and drive electrode pairs appropriately located around the trapping pockets. Agarose droplets capable of encapsulating biological samples were successfully trapped in the trapping pockets due to the difference in flow resistance between the main and side channels. Target droplets were selectively extracted from the pockets by the dielectrophoretic force generated between the electrodes under an applied voltage of 500 V. During their extraction from the trapping pockets, the droplets and their contents were exposed to an electric field for 400-800 ms. To evaluate whether the applied voltage could potentially damage the biological samples, the growth rates of Escherichia coli cells in the droplets, with and without a voltage applied, were compared. No significant difference in the growth rate was observed. The developed device enables the screening of encapsulated single cells and the selective extraction of target droplets.
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Eritrodermia Ictiosiforme Congénita , Errores Innatos del Metabolismo Lipídico , Enfermedades Musculares , Humanos , Enfermedades Musculares/diagnóstico por imagen , Enfermedades Musculares/genética , Errores Innatos del Metabolismo Lipídico/genética , Mutación , Músculo Esquelético , Aciltransferasas , Lipasa/genéticaRESUMEN
Aim: The study aimed to determine the current status of face mask use, deep body temperature measurement, and active cooling in patients suffering from heat stroke and heat exhaustion in Japan. Methods: This was a prospective, observational, multicenter study using data from the Heatstroke STUDY 2020-2021, a nationwide periodical registry of heat stroke and heat exhaustion patients. Based on the Bouchama heatstroke criteria, we classified the patients into two groups: severe and mild-to-moderate. We compared the outcomes between the two groups and reclassified them into two subgroups according to the severity of the illness, deep body temperature measurements, and face mask use. Cramer's V was used to determine the effect sizes for a comparison between groups. Results: Almost all patients in this study were categorized as having degree III based on the Japanese Association for Acute Medicine heatstroke criteria (JAAM-HS). However, the severe group was significantly worse than the mild-to-moderate group in outcomes like in-hospital death and modified Rankin Scale scores, when discharged. Heat strokes had significantly higher rates of active cooling and lower mortality rates than heat stroke-like illnesses. Patients using face masks often use them during labor, sports, and other exertions, had less severe conditions, and were less likely to be young male individuals. Conclusions: It is suggested that severe cases require a more detailed classification of degree III in the JAAM-HS criteria, and not measuring deep body temperature could have been a factor in the nonperformance of active cooling and worse outcomes.
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We developed two multiplex polymerase chain reactions (PCRs) for the detection of extended-spectrum ß-lactamases (ESBLs), plasmid-mediated AmpC ß-lactamases, aac(6')-Ib gene, and integrase genes (intI1, intI2, and intI3) in class 1, 2, and 3 integrons in Gram-negative bacteria. We evaluated the PCRs using 109 Gram-negative isolates from non-organic (ANO) and organic (AO) vegetables and fruits. Screening of ANO substances identified five SHV, one TEM-1, one CTX-M, 20 AmpC-CS, and two intI1 positives. DNA sequencing revealed CTX-M in Pantoea spp. was blaRANH-2, a plasmid-mediated CTX-M related ESBL gene only found in Rahnella spp. Of the 20 AmpC-CS positives, 10 were CMY/MIR/ACT/EC (3 new variants), eight were ACT, one was AZECL, and one was new Pseudomonas-related AmpC family. Screening of AO substances identified 11 SHV, two TEM-1, three CTX-M (one OXY-2, two CTX-M-14/-15), two OXA-9, 13 AmpC-CS and one intI1 positives. The 13 AmpC-CS positives were five CMY/MIR/ACT/EC, three ACT, one MOX-12 variant, and four ADC (one ADC-25 and three new variants). We developed a rapid, easy-to-perform, low-cost, and reliable multiplex PCR system for screening clinically relevant ß-lactamases and integrons in Gram-negative bacteria. We showed the prevalence of ESBLs and AmpC ß-lactamases among our panel of ampicillin-resistant Gram-negative strains and detection of NDM and OXA carbapenemases.
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The Stroop effect is a classical, well-known behavioral phenomenon in humans that refers to robust interference between language and color information. It remains unclear, however, when the interference occurs and how it is resolved in the brain. Here we show that the Stroop effect occurs during perception of color-word stimuli and involves a cross-hemispheric, excitatory-inhibitory loop functionally connecting the lateral prefrontal cortex and cerebellum. Participants performed a Stroop task and a non-verbal control task (which we term the Swimmy task), and made a response vocally or manually. The Stroop effect involved the lateral prefrontal cortex in the left hemisphere and the cerebellum in the right hemisphere, independently of the response type; such lateralization was absent during the Swimmy task, however. Moreover, the prefrontal cortex amplified cerebellar activity, whereas the cerebellum suppressed prefrontal activity. This fronto-cerebellar loop may implement language and cognitive systems that enable goal-directed behavior during perceptual conflicts.
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Encéfalo , Corteza Prefrontal , Humanos , Test de Stroop , Tiempo de Reacción/fisiología , Encéfalo/fisiología , Corteza Prefrontal/fisiología , Cerebelo , Imagen por Resonancia MagnéticaRESUMEN
BACKGROUND: The antioxidant and anti-inflammatory effects of resveratrol have been reported previously. Particularly, monomeric trans-resveratrol has been demonstrated to produce positive effects in various pathological processes. We reported previously that resveratrol dimer-rich melinjo extract, among others, caused bone healing, decreased local oxidative damage, and activated antioxidants nuclear factor erythroid 2-related factor 2 (Nrf2) pathways in a mouse model of experimentally induced periodontitis (EP). This study aimed to compare the bone-healing effects of the resveratrol monomer to the resveratrol dimer (gnetin C found in melinjo seed extract) in a model of EP and investigate the involvement of Nrf2 for effects of either form of resveratrol. METHODS: EP was induced experimentally in mice by placement of a 9 - 0 silk ligature around the left second molar. Mice received 10 mg/kg of either resveratrol monomer or dimer intraperitoneally on day 15 after induction of EP. The bone level around the ligated teeth was measured over time, and levels of proinflammatory cytokines and oxidative stress were measured in the periodontal tissues around the ligated teeth. RESULTS: Resveratrol dimer induced greater periodontal bone healing as compared to that related to use of the resveratrol monomer. It appears that healing of periodontal bone in either group was likely related to master regulation of antioxidant nuclear factor erythroid 2-related factor 2 (Nrf2) significantly. Downregulation of IL-1ß, a proinflammatory cytokine was also demonstrated in the resveratrol dimer group. CONCLUSION: Our results showed that administration of resveratrol in either dimer form or the monomeric form reduced periodontal bone loss with greater inhibition of bone loss being demonstrated in the dimer group as compared to the monomer group and that these effects were related in all likelihood to decreased oxidative stress and hence reduction in local inflammation.
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Pérdida de Hueso Alveolar , Periodontitis , Ratones , Animales , Resveratrol , Factor 2 Relacionado con NF-E2 , Antioxidantes/farmacología , Periodontitis/metabolismo , Modelos Animales de Enfermedad , Citocinas/metabolismoRESUMEN
A 64-year-old man presented with left upper limb weakness and dysesthesia for 4 months. Magnetic resonance imaging demonstrated swelling from the 6th-8th left cervical nerve roots to the left brachial plexus. The serum IgG4 level was elevated (762.7 mg/dL). 18F-FDG-PET showed high uptake in the mediastinal lymph nodes, and biopsy revealed infiltration of IgG4-positive plasma cells. We diagnosed IgG4-related neuropathy, and steroid therapy administration improved the symptoms. IgG4-related disease should be considered in the differential diagnosis of peripheral nerve swellings. If biopsy of the disordered nerves is difficult, lymph nodes or other organs should be considered.
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We describe the synthesis and characterization of a photoactivated boron-based Lewis acid catalyst based on a cage-shaped triphenolic ligand with three pyrenylmethyl moieties. The obtained cage-shaped borate functioned as a photoactivated Lewis acid catalyst thanks to the flexible three pyrenylmethyl moieties. The deformation of the cage-shaped scaffold driven by intramolecular excimer formations of the pyrenes is a critical factor in realizing the photoactivation. Mannich-type reactions and glycosylations significantly were accelerated under 370â nm light irradiations. It is noteworthy that various glycosyl fluorides, which are not easily activated in photocatalytic systems due to their high C-F bond stability, are activated by the photoimproved catalytic activity of the catalyst.
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Boratos , Ácidos de Lewis , Ácidos de Lewis/química , Glicosilación , Catálisis , BoroRESUMEN
Objective: To evaluate patient acceptability and bowel preparation efficacy of sodium picosulfate-magnesium citrate (PICOPREP) for colonoscopy. Methods: A questionnaire survey regarding the patient acceptability of bowel preparation agent PICOPREP was administered to 54 patients, and its efficacy was evaluated using the Ottawa Bowel Preparation Scale (OBPS). Results: Eighteen (33.3%) participants reported that PICOPREP is very easy to drink, 30 (55.5%) easy, four (7.4%) acceptable, one (1.9%) difficult, and one (1.9%) very difficult. The flavor was very good as reported by eight (14.8%) participants, good by 25 (46.3%), neutral by 20 (37.0%), bad by one (1.9%), and very bad by none. The number of patients who requested PICOPREP was 42 (77.7%), indicating its high acceptability. Evaluation of the OBPS score showed that the rectosigmoid colon had significantly better polyethylene glycol (PEG) scores than PICOPREP, but the entire colon did not show a significant difference between PICOPREP and PEG scores (1.09 ± 0.65 vs. 1.17 ± 0.76, p = 0.632 in the right colon; 0.48 ± 0.52 vs. 0.72 ± 0.66, p = 0.079 in the mid colon, 0.93 ± 0.49 vs. 0.63 ± 0.52, p = 0.012 in the rectosigmoid colon, and 3.28 ± 1.70 vs. 3.20 ± 1.90, p = 0.836 in the entire colon). Conclusion: PICOPREP is considered as one of the important options due to its good patient acceptability and high efficacy similar to PEG.